The overall aim of this research project is to elucidate in greater detail than is now available the mechanism of catalase action in the oxidation of ethanol and methanol. The catalase pathway of alcohol oxidation does not derange the redox balance of the cell. Its molecular statistics, intracellular localization, and the metabolic control parameters involved can be dealt with quantitatively, primarily by methods developed in this laboratory. The interaction of this pathway with the more active pathway of alcohol oxidation by alcohol dehydrogenase will be explored, and activators and inhibitors which may shift the oxidation towards the catalase pathway will be sought, with the ultimate goal of controlling to some degree the redox imbalance that is characteristic of acute and chronic alcoholism and alleviating the metabolic difficulties inherent in the alcoholic state. These studies will range from the mechanism of catalase action in the isolated purified enzyme, through crystalline suspensions similar to the state of catalase in the peroxisome, the peroxisome itself and the mitocondrial-peroxisomal fraction, to the readout of metabolic states in the perfused organ, particularly the liver, and in exposed organs of the intact, anesthetized animal. Because the methods employed are amenable to the study of biopsy material and to the non-destructive readout of biochemical information from the intact organ in vivo, the research plan and ultimate goals of this project are perhaps more closely allied to a direct application to the problems of alcoholism than would be feasible with more restricted approaches of biochemistry and biophysics to the basic nature of the alcoholic state.